I plan to study genetic variants affecting early events in the development of the nervous system of Drosophila, mutations and deletions which cause an arrest of development in these cells or an apparent failure of crucial cell interactions, in an effort to understand the nature of the genetic information directing this process. With internally marked genetic mosaics, I will determine the cells or tissues that comprise the primary site of action of the mutant or deleted genes. For those variants that are currently defined only by deletions, I will isolate new mutations uncovered by them, constructing new chromosomal insertions and translocations where necessary. Mutant phenotypes will be characterized histologically, and multiple alleles of the same locus will be studied with respect to their interactions and range of effects. In a related approach, I will study alterations in cell surface components associated with these mutations, in an effort to identify molecules that might mediate cell interactions. To this end, I will isolate monoclonal antibodies which recognize antigenic differences between mutant and wild-type embryonic cells. I will then characterize genetically the antigens recognized by these antibodies in order to determine whether they are the structural products of the mutant genes used in the screen, in which case I will have made the first step towards a biochemical study of the developmental gene. If they are not products of the structural locus but are only dependent upon it for their expression, then I will determine their structural loci either by segmental aneuploidy, or by searching for and mapping natural polymorphisms for the antigens. Identification of these new genes will then expand the ability to examine gnetic influences on the developing nervous system. The understanding of genetic control mechanisms involved in early developmental events, which is feasible with the genetic leverage available in Drosophila, would contribute tangibly to our ability to understand the etiology of hereditary diseases of humans, many of which affect the nervous system.